Therapeutic benefits of proning to improve pulmonary gas exchange in severe respiratory failure: Focus on fundamentals of physiology

NEW FINDINGS: What is the topic of this review? The use of proning for improving pulmonary gas exchange in critically ill patients. What advances does it highlight? Proning places the lung in its ‘natural’ posture, and thus optimises the ventilation‐perfusion distribution, which enables lung protective ventilation and the alleviation of potentially life‐threatening hypoxaemia in COVID‐19 and other types of critical illness with respiratory failure. ABSTRACT: The survival benefit of proning patients with acute respiratory distress syndrome (ARDS) is well established and has recently been found to improve pulmonary gas exchange in patients with COVID‐19‐associated ARDS (CARDS). This review outlines the physiological implications of transitioning from supine to prone on alveolar ventilation‐perfusion ([Formula: see text]) relationships during spontaneous breathing and during general anaesthesia in the healthy state, as well as during invasive mechanical ventilation in patients with ARDS and CARDS. Spontaneously breathing, awake healthy individuals maintain a small vertical (ventral‐to‐dorsal) [Formula: see text] ratio gradient in the supine position, which is largely neutralised in the prone position, mainly through redistribution of perfusion. In anaesthetised and mechanically ventilated healthy individuals, a vertical [Formula: see text] ratio gradient is present in both postures, but with better [Formula: see text] matching in the prone position. In ARDS and CARDS, the vertical [Formula: see text] ratio gradient in the supine position becomes larger, with intrapulmonary shunting in gravitationally dependent lung regions due to compression atelectasis of the dorsal lung. This is counteracted by proning, mainly through a more homogeneous distribution of ventilation combined with a largely unaffected high perfusion dorsally, and a consequent substantial improvement in arterial oxygenation. The data regarding proning as a therapy in patients with CARDS is still limited and whether the associated improvement in arterial oxygenation translates to a survival benefit remains unknown. Proning is nonetheless an attractive and lung protective manoeuvre with the potential benefit of improving life‐threatening hypoxaemia in patients with ARDS and CARDS

Gut Microbiota in Human Adults with Type 2 Diabetes Differs from Non-Diabetic Adults

Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control. was highly enriched in diabetic compared to non-diabetic persons (P = 0.02) and positively correlated with plasma glucose (P = 0.04).The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies to control metabolic diseases by modifying the gut microbiota

Agents intervening against delirium in the intensive care unit trial-Protocol for a secondary Bayesian analysis

Background Delirium is highly prevalent in the intensive care unit (ICU) and is associated with high morbidity and mortality. The antipsychotic haloperidol is the most frequently used agent to treat delirium although this is not supported by solid evidence. The agents intervening against delirium in the intensive care unit (AID-ICU) trial investigates the effects of haloperidol versus placebo for the treatment of delirium in adult ICU patients. Methods This protocol describes the secondary, pre-planned Bayesian analyses of the primary and secondary outcomes up to day 90 of the AID-ICU trial. We will use Bayesian linear regression models for all count outcomes and Bayesian logistic regression models for all dichotomous outcomes. We will adjust for stratification variables (site and delirium subtype) and use weakly informative priors supplemented with sensitivity analyses using sceptical priors. We will present results as absolute differences (mean differences and risk differences) and relative differences (ratios of means and relative risks). Posteriors will be summarised using median values as point estimates and percentile-based 95% credibility intervals. Probabilities of any benefit/harm, clinically important benefit/harm and clinically unimportant differences will be presented for all outcomes. Discussion The results of this secondary, pre-planned Bayesian analysis will complement the primary frequentist analysis of the AID-ICU trial and facilitate a nuanced and probabilistic interpretation of the trial results.Peer reviewe

Type 2 Diabetes Is Associated with Altered NF-κB DNA Binding Activity, JNK Phosphorylation, and AMPK Phosphorylation in Skeletal Muscle after LPS

Systemic inflammation is often associated with impaired glucose metabolism. We therefore studied the activation of inflammatory pathway intermediates that interfere with glucose uptake during systemic inflammation by applying a standardised inflammatory stimulus in vivo. After ethical approval, informed consent and a thorough physical examination, 10 patients with type 2 diabetes and 10 participants with normal glucose tolerance (NGT) were given an intravenous bolus of E. coli lipopolysaccharide (LPS) of 0.3 ng/kg. Skeletal muscle biopsies and plasma were obtained at baseline and two, four and six hours after LPS. Nuclear factor (NF)-κB p65 DNA binding activity measured by ELISA, tumor necrosis factor-α and interleukin-6 mRNA expression analysed by real time reverse transcription polymerase chain reaction, and abundance of inhibitor of NF-κB (IκB)α, phosphorylated c-Jun-N-terminal kinase (JNK), AMP-activated protein kinase (AMPK), and acetyl-CoA carboxylase measured by Western blotting were detected in muscle biopsy samples. Relative to subjects with NGT, patients with type 2 diabetes exhibited a more pronounced increase in NF-κB binding activity and JNK phosphorylation after LPS, whereas skeletal muscle cytokine mRNA expression did not differ significantly between groups. AMPK phosphorylation increased in volunteers with NGT, but not in those with diabetes. The present findings indicate that pathways regulating glucose uptake in skeletal muscle may be involved in the development of inflammation-associated hyperglycemia. Patients with type 2 diabetes exhibit changes in these pathways, which may ultimately render such patients more prone to develop dysregulated glucose disposal in the context of systemic inflammation

New-onset atrial fibrillation in critically ill adult patients—an SSAI clinical practice guideline

Publisher Copyright: © 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.Background: Acute or new-onset atrial fibrillation (NOAF) is the most common cardiac arrhythmia in critically ill adult patients, and observational data suggests that NOAF is associated to adverse outcomes. Methods: We prepared this guideline according to the Grading of Recommendations Assessment, Development and Evaluation methodology. We posed the following clinical questions: (1) what is the better first-line pharmacological agent for the treatment of NOAF in critically ill adult patients?, (2) should we use direct current (DC) cardioversion in critically ill adult patients with NOAF and hemodynamic instability caused by atrial fibrillation?, (3) should we use anticoagulant therapy in critically ill adult patients with NOAF?, and (4) should critically ill adult patients with NOAF receive follow-up after discharge from hospital? We assessed patient-important outcomes, including mortality, thromboembolic events, and adverse events. Patients and relatives were part of the guideline panel. Results: The quantity and quality of evidence on the management of NOAF in critically ill adults was very limited, and we did not identify any relevant direct or indirect evidence from randomized clinical trials for the prespecified PICO questions. We were able to propose one weak recommendation against routine use of therapeutic dose anticoagulant therapy, and one best practice statement for routine follow-up by a cardiologist after hospital discharge. We were not able to propose any recommendations on the better first-line pharmacological agent or whether to use DC cardioversion in critically ill patients with hemodynamic instability induced by NOAF. An electronic version of this guideline in layered and interactive format is available in MAGIC: https://app.magicapp.org/#/guideline/7197. Conclusions: The body of evidence on the management of NOAF in critically ill adults is very limited and not informed by direct evidence from randomized clinical trials. Practice variation appears considerable.Peer reviewe